WDR83OS

Last update 08 May 2025

Basic Info

Synonyms

Asterix, C19orf56, PAT complex subunit Asterix

+ [7]

Introduction

Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:12475939, PubMed:32814900, PubMed:36261522). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:32814900, PubMed:36261522). Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein (By similarity). Within the PAT subcomplex, WDR83OS/Asterix binds to and redirects the substrate to a location behind the SEC61 complex (By similarity).

100 Clinical Results associated with WDR83OS

100 Translational Medicine associated with WDR83OS

0 Patents (Medical) associated with WDR83OS

Literatures (Medical) associated with WDR83OS

27 Feb 2025·Horticulture Research

Integrative analysis of genome-wide association studies of polyphenols in apple fruits identifies the MdDof2.4-MdPAT10 module that promotes procyanidin accumulation

Article

Author: Cui, Yilin ; Ma, Fengwang ; Zhan, Xiangqiang ; Li, Lei ; Gao, Cai ; Fan, Tianle ; Li, Zhongxing ; Niu, Chundong ; Yang, Peizhi ; Liu, Zeyuan ; Guan, Qingmei ; Qian, Qian ; Cheng, Mengjie

AbstractPolyphenols represent a significant class of nutrients in apples, contributing to human health and well-being. Among these, procyanidins stand out as the most prevalent polyphenolic compounds in apple fruits. These compounds are abundant in wild apples and generally low in modern apple cultivars. Therefore, it is crucial to identify and recover genetically lost genes that regulate polyphenol accumulation in order to improve the apple quality. To achieve this, we conducted a genome-wide association study (GWAS) on 15 traits related to polyphenol content, utilizing 134 Malus accessions. We identified 1204 marker–trait associations (MTAs) and 840 candidate genes, including known polyphenol biosynthetic and regulatory genes, such as MYB7, TT4, and HCT/HQT. Notably, we pinpointed a protein S-acyl transferase 10 (PAT10), which is significantly associated with procyanidin content. Through experiments with transgenic calli, we determined that apple (Malus domestica) MdPAT10 positively regulated procyanidin accumulation. Furthermore, we identified a 51-bp insertion variant (In-868) on the promoter of the PAT10, which influences its expression. Both a yeast one-hybrid (Y1H) assay and an electrophoretic mobility shift assay (EMSA) revealed that MdDof2.4 was able to bind to the promoter of MdPAT10 containing In-868 (MdPAT10proIn-868), but not to the promoter of MdPAT10 without In-868 (MdPAT10pro). Moreover, MdDof2.4 promoted MdPAT10 (with MdPAT10proIn-868) expression and increased procyanidin accumulation in fruits. Overall, our results enhance the understanding of the biosynthetic regulation of apple polyphenols and provide a theoretical foundation and genetic resources for breeding apple varieties with optimal polyphenol content.

01 Nov 2024·The American Journal of Human Genetics

Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia

Article

Author: Posey, Jennifer E. ; Huber, Ilka ; Trimouille, Aurélien ; Busk, Øyvind L. ; Lupski, James R ; Wali, Sami ; Bauer, Peter ; Ghayoor Karimiani, Ehsan ; Mitani, Tadahiro ; Shervin Badv, Reza ; Holla, Øystein L ; Tveten, Kristian ; Houlden, Henry ; Beiraghi Toosi, Mehran ; Zifarelli, Giovanni ; Barish, Scott ; Marafi, Dana ; Maroofian, Reza ; Alkuraya, Fowzan S. ; Fatih, Jawid M ; Alswaid, Abdulrahman ; Petree, Cassidy ; Lupski, James R. ; Al Safar, Ayat ; Gezdirici, Alper ; Huang, Kevin ; Biderman Waberski, Marta ; Busk, Øyvind L ; Holla, Øystein L. ; Varshney, Gaurav K ; Varshney, Gaurav K. ; Akhondian, Javad ; Lin, Sheng-Jia ; Alkuraya, Fowzan S ; von der Lippe, Charlotte ; Eghbal, Fatemeh ; Najarzadeh Torbati, Paria ; Calame, Daniel G ; Alhebby, Hamoud ; Fatih, Jawid M. ; Calame, Daniel G. ; Pehlivan, Davut ; Posey, Jennifer E

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia.

03 Nov 2022·Nature

Mechanism of an intramembrane chaperone for multipass membrane proteins

Article

Author: Hegde, Ramanujan S ; Keenan, Robert J ; Smalinskaitė, Luka ; Lewis, Aaron J O ; Kim, Min Kyung

Multipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels and enzymes^1,2. How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum is not well understood². The prevailing model posits that each transmembrane domain (TMD) of a multipass protein successively passes into the lipid bilayer through a front-side lateral gate of the Sec61 protein translocation channel^3-9. The PAT complex, an intramembrane chaperone comprising Asterix and CCDC47, engages early TMDs of multipass proteins to promote their biogenesis by an unknown mechanism¹⁰. Here, biochemical and structural analysis of intermediates during multipass protein biogenesis showed that the nascent chain is not engaged with Sec61, which is occluded and latched closed by CCDC47. Instead, Asterix binds to and redirects the substrate to a location behind Sec61, where the PAT complex contributes to a multipass translocon surrounding a semi-enclosed, lipid-filled cavity¹¹. Detection of multiple TMDs in this cavity after their emergence from the ribosome suggests that multipass proteins insert and fold behind Sec61. Accordingly, biogenesis of several multipass proteins was unimpeded by inhibitors of the Sec61 lateral gate. These findings elucidate the mechanism of an intramembrane chaperone and suggest a new framework for multipass membrane protein biogenesis at the endoplasmic reticulum.

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WDR83OS

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